Versatile Electrochemical Biosensor Based on the Target-Controlled Capture and Release of DNA Nanotubes for the Ultrasensitive Detection of Multiplexed Biomarkers

Herein, an ultrasensitive and versatile electrochemical biosensor was developed through the target-controlled capture and release of signal probe-loaded DNA nanotube for the ultrasensitive detection of two different types of cancer-related biomarkers, microRNA-21 (miRNA-21) and glutathione (GSH). In this system, target 1 (miRNA-21) first triggered duplex-specific nuclease (DSN)-assisted recycle amplification to generate numerous disulfide-linked DNA strands (DL), which could effectively capture DNA nanotube to immobilize methylene blue (MB) to produce remarkable electrochemical signals and achieve the ultrasensitive detection of miRNA-21 with a detection limit down to 32.6 aM. Furthermore, in the presence of target 2 (GSH), the electrochemical signal was significantly reduced by a thiol- disulfide bond exchange reaction on DL to release MB- immobilized DNA nanotubes away from the sensing interface, which enabled the sensitive analysis of GSH with a detection limit of 0.379 n.M. Impressively, this strategy could achieve ultrasensitive detection of different types of biomarkers to prominently lessen false-positive responses from the current sensing methods toward a single biomarker or the same type of biomarker and remarkably heighten the accuracy and precision of early cancer diagnosis. Meanwhile, the proposed electrochemical biosensor made it possible to realize the regenerative analysis of targets over four times without extra fuel, which could conspicuously improve the analytical efficiency compared with that of traditional biosensing assays. As a result, this study might open up novel insights to design a versatile and multifunctional sensing platform and encourage deeper exploration for detecting different types of biomarkers in the fields of early disease diagnosis and biochemical research.

Automated summary

This study presents the development of an ultrasensitive and versatile electrochemical biosensor for the detection of cancer-related biomarkers (miRNA-21 and GSH) through target-controlled capture and release of signal probe-loaded DNA nanotubes. The biosensor demonstrated high sensitivity and the ability to detect different types of biomarkers, reducing false-positive responses and improving the accuracy and precision of early cancer diagnosis. The proposed biosensor also allowed for regenerative analysis of targets, enhancing analytical efficiency.